A Study of TAS-120 in Patients With Advanced Solid Tumors

This is an open-label, nonrandomized, Phase 1/2 study for the fibroblast growth factor receptor (FGFR) inhibitor futibatinib (TAS-120). The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, and anti-tumor activity of futibatinib in patients with advanced solid tumors with and without genomic FGF/FGFR abnormalities. The study will be conducted in 3 parts: 1. Dose escalation portion to determine the -Maximum Tolerated Dose and/ or Recommended Phase 2 Dose of futibatinib. 2. Phase 1 expansion portion to further evaluate the safety and efficacy of futibatinib in patients with tumors harboring FGF/FGFR aberrations, including patients with cholangiocarcinoma (CCA), primary central nervous system tumors, urothelial carcinoma, breast cancer, gastric cancer. 3. Phase 2 study portion to confirm objective response rate of futibatinib in intrahepatic CCA patients with tumors harboring FGFR2 gene rearrangements (incl fusions).

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Provide written informed consent
2. Age ≥ 18 years of age
3. Has histologically or cytologically confirmed, locally advanced or metastatic cancer
4. The following specific criteria for each study portion

   Phase 1 (Dose Escalation):
   * Patients with any type of solid tumor
   * Disease progression following standard therapies or intolerant to prior standard therapies

   Phase 1 (Dose Expansion)
   * Have at least one FGF/FGFR aberration
   * Disease progression following standard therapies or were intolerant to prior standard therapies (including prior FGFR inhibitors).
   * Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or Response Assessment in Neuro-Oncology criteria (2010) for brain tumors.
   * Patients with any of the following tumor types

     * Patients with intrahepatic or extrahepatic CCA harboring FGFR2 gene fusions or other FGFR2 aberrations
     * Patients with primary CNS tumors
     * Patients with advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations
     * Patients with breast cancer or gastric cancer
     * Patients with other solid tumor types harboring FGFR gene fusions or activating mutations
     * Patients with solid tumor types and other FGF/FGFR alterations not listed above

   Phase 2
   * Patients with iCCA and FGFR2 gene rearrangements (incl fusions)
   * Have been treated with at least one prior systemic gemcitabine and platinum-based chemotherapy
   * Must have documentation of radiographic progression of disease
   * No prior FGFR inhibitor
   * Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009)
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
6. Adequate organ function.

Exclusion Criteria:

1. History and/or current evidence of clinically significant non-tumor related alteration of calcium-phosphorus homeostasis.
2. History and/or current evidence of clinically significant ectopic mineralization/calcification.
3. History and/or current evidence of clinically significant retinal disorder
4. A serious illness or medical condition(s)
5. Pregnant or breast-feeding female

• DERIVEDGoyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, Abrams TA, Furuse J, Kelley RK, Cassier PA, Klumpen HJ, Chang HM, Chen LT, Tabernero J, Oh DY, Mahipal A, Moehler M, Komatsu Y, Ahn DH, Epstein RS, Halim AB, Wacheck V, He Y, Liu M, Benhadji KA, Bridgewater JA; FOENIX-CCA2 Study Investigators. Plain language summary of the FOENIX-CCA2 study: futibatinib for people with advanced bile duct cancer. Future Oncol. 2024;20(36):2811-2822. doi: 10.1080/14796694.2024.2364504. Epub 2024 Jun 17. PMID 38884254
• DERIVEDDiPeri TP, Zhao M, Evans KW, Varadarajan K, Moss T, Scott S, Kahle MP, Byrnes CC, Chen H, Lee SS, Halim AB, Hirai H, Wacheck V, Kwong LN, Rodon J, Javle M, Meric-Bernstam F. Convergent MAPK pathway alterations mediate acquired resistance to FGFR inhibitors in FGFR2 fusion-positive cholangiocarcinoma. J Hepatol. 2024 Feb;80(2):322-334. doi: 10.1016/j.jhep.2023.10.041. Epub 2023 Nov 14. PMID 37972659
• DERIVEDGoyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, Abrams TA, Furuse J, Kelley RK, Cassier PA, Klumpen HJ, Chang HM, Chen LT, Tabernero J, Oh DY, Mahipal A, Moehler M, Mitchell EP, Komatsu Y, Masuda K, Ahn D, Epstein RS, Halim AB, Fu Y, Salimi T, Wacheck V, He Y, Liu M, Benhadji KA, Bridgewater JA; FOENIX-CCA2 Study Investigators. Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. N Engl J Med. 2023 Jan 19;388(3):228-239. doi: 10.1056/NEJMoa2206834. PMID 36652354
• DERIVEDBahleda R, Meric-Bernstam F, Goyal L, Tran B, He Y, Yamamiya I, Benhadji KA, Matos I, Arkenau HT. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1-4 inhibitor in patients with advanced solid tumors. Ann Oncol. 2020 Oct;31(10):1405-1412. doi: 10.1016/j.annonc.2020.06.018. Epub 2020 Jul 2. PMID 32622884